The mechanisms of motor end-plate depolarization due to a cholinesterase-inhibiting drug / by W.W. Douglas and W.D.M. Paton.

  • Douglas, W. W.
Date:
[1954?]
Catalogue details

Licence: In copyright

Credit: The mechanisms of motor end-plate depolarization due to a cholinesterase-inhibiting drug / by W.W. Douglas and W.D.M. Paton. Source: Wellcome Collection.

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    the injection of the TEPP, the usual effects of injection of an anticholin¬ esterase into this preparation were observed, i.e. fasciculation and potentiation of the twitch succeeded by partial or complete paralysis according to the dose. Thus, TEPP must be supposed to lack any significant direct muscle- stimulant action; if it exists it is not greater than yqo <jth that of acetylcholine. But it remains to be explained how TEPP produces a depolarization of the unstimulated muscle in some respects so deceptively similar to that of a directly acting drug. The most obvious explanation was that it acts by pre¬ serving acetylcholine formed at the terminations of the motor nerve. To test this possibility, we carried out experiments on denervated muscles. Fig. 6. Graph of depolarization of end-plate region of cat’s denervated gracilis muscle after TEPP 10 mg/kg intravenously. The denervated gracilis muscle In two experiments, the effect of 500 ptg/kg of TEPP on a muscle denervated 4 and 6 days previously was hardly detectable. Stimulation of the peripheral stump of the nerve to the muscle, or of the muscle itself in the neighbourhood of the end-plate zone, in both experiments failed to cause any depolarization and confirmed that significant acetylcholine release from nerve elements in the muscle was absent. But in these animals and in each of two others, depolarization occurred with large doses of TEPP (10-20 mg/kg). This depolarization was much slower both in onset and in rate of rise, and smaller than in the innervated preparation (Fig. 6) and in degree was roughly com¬ parable to that produced by 1 mg/kg TEPP in the normal muscle. It was clear